Pharmacological activation of adenosine signaling promotes ?-cell proliferation independently of an apoptotic microenvironment. (A) Schema of the analysis of ?-cell proliferation in control zebrafish larvae and larvae subjected to ?-cell ablation or ?-cell ablation. Ablation was carried out by exposing the nitroreductase (NTR)-expressing transgenics to metronidazole (MTZ) from 3 to 4 days post fertilization (dpf). Islets were analyzed by confocal microscopy at 5 dpf. (B?G) Representative pictures of proliferating ?-cells (arrowheads) in islets of Tg(ins:venus-geminin) zebrafish treated with DMSO or NECA from 4 to 5 dpf in the presence or absence of ?-cell ablation (D?E) or ?-cell ablation (F?G). ?-cell ablation was achieved by crossing the Tg(ins:venus-geminin) zebrafish with Tg(ins:flag-NTR) zebrafish and treating them with MTZ; ?-cell ablation by crossing them with Tg(sst:NTR) zebrafish and treating them with MTZ. (H) ?-cell proliferation in the absence of cell ablation (CTL), and after ?-cell or ?-cell ablation. Each condition was normalized (DMSO = 1), allowing comparison of fold changes. Absolute numbers are shown in Figure S1. n = 13?32; scale bars: 10 ?m; **p < 0.01; ****p < 0.0001.